This invention relates mass spectrometry and an in particular to a method of generating ion pulses (sometimes referred to as ion xe2x80x9cpacketsxe2x80x9d) from an ion beam.
Time-of-flight mass spectrometers (TOFMS) are widely used to identify molecular structures in chemistry, bioscience, drug discovery and the like. The advantages of using TOFMS include its unlimited mass range, precise mass determination and the ability to detect transient signals.
For TOFMS analysis, ions are detected in the form of short bunches (or xe2x80x9cpacketsxe2x80x9d) of several nanoseconds in duration. These short ion bunches are produced by either pulsed ion generation methods such as pulsed laser desorption/ionization (LDI) or by extracting them from an ion beam which is continuously generated. Electrospray (ES) and chemical ionization (CI) for instance, are continuous ionization techniques widely used for drug and biomolecule analysis. Continuous ionization by inductively coupled plasma (ICP) is an advanced technique for elemental analysis.
To produce ion packets from a continuous ion beam, a device as shown in FIG. 1 is usually utilized. That device (referred to as an ion pulser 16) normally consists of three or more parallel-arranged electrodes. One electrode R is a repeller electrode in the form of a solid metal plate, while the others such as P0 and P1 are ring-shaped electrodes with central openings each of typically 20 mm in diameter and each having a highly transparent metal mesh 24, 25 respectively (grid) covering the opening. The ion packet production occurs via two separated steps:
1. Ion filling period: A continuous ion beam 14 generated by an ion source 10 (which may be ES, CI, ICP or any other ion source generating a continuous beam) is directed into the region between a repeller electrode R and across grid 24 of electrode P0 (which is parallel to electrode R) and is collected at a collector electrode (basically the same as electrode 146 shown in FIG. 4). The travel direction of ions is parallel to the electrodes. During this period, the voltages applied to repeller R and electrode P0 are nearly the same, as indicated by pulse OFF regions 43 of a typical waveform 40 applied between R and P0 (see FIG. 2A). This results in a time 46 during which ions can fill the region over grid 24 and continue to pass thereover for collection by a collection electrode beyond R and P0 The filling time depends on the ion energy and mass of the ions to be analyzed and is generally of several hundred nanoseconds to several microseconds. By xe2x80x9cfilling timexe2x80x9d in this context is referenced the time it takes to establish the beam containing the ions of highest predetermined mass of interest across grid 24.
2. When the region across grid 24 is filled with ions of interest, an electrical pulse (extraction pulse) 42 is applied to repeller R to form an accelerating field between R and P0. Ions are bundled into a packet 28 and accelerated in the perpendicular direction of the original travel for provision to a mass analyzer section of a mass spectrometer. The duration 44 of the extraction pulse is determined by the time required to accelerate ions of all mass out of the ion pulser, i.e. to pass grid 24 and is generally 1 to 3 microseconds in a conventional TOFMS.
Steps 1 and 2 above are repeated during the entire sample analysis, and the repetition rate is dependent of the time for ions of maximum molecular weight of interest to reach a detector 180 of the mass analyzer. The flight time for the ions in the mass analyzer is a function of mass to charge ratio of ions and many other mechanical and electrical parameters as well. For a typical mass analyzer in ICP detection, the maximum flight time is about 40 xcexcs.
In a conventional TOFMS, the extraction pulse is turned off after 1 to 3 xcexcs and ions begin to refill the ion pulser. Up to the time the next extraction pulse is applied, there is a period that ions can xe2x80x9cleakxe2x80x9d from the ion pulser and be accelerated toward the detector. The leakage is a result of ion diffusion and space charge repulsion. Leakage ions 32 generate a continuous background noise in an acquired mass spectrum and limit signal-to-noise ratio, and hence the sensitivity of detection. That is, referring to FIG. 2B, ions continue to flow across grid 24 during pulse OFF times (which are relatively long compared to the ON times), and only that portion 58 of ions present just before application of pulse 42 is extracted. Ions during the time 54 of each pulse cycle have the potential of leaking into the analyzer region and increasing background noise.
U.S. Pat. No. 5,654,543 describes a method to reduced the above unwanted background noise by utilized an energy discrimination device. Using this method, unwanted species can be effectively blocked if they remain electrically charged. However, in many applications, large amounts of ions are sampled. These ions can become neutralized due to collisions with residual species in the vacuum chamber. Such neutral species retain the velocity of the ions and can reach the detector without being blocked by the energy discriminator. The resulting background noise originated from such neutral species has been experimentally observed (see P. Mahoney et al., J Am Soc Mass Spectrom, 8, 166-124 (1997).
It would be desirable then if a means could be found of reducing background noise resulting from the above described leakage ions. It would further be desirable if such a means was relatively simple to construct and use.
The present invention then, provides a method for reducing the above described background noise. In one aspect, the method provides an ion packet to an analyzer section of a mass spectrometer from an ion beam. A field pulse is applied to extract an ion packet from the beam at a sideways direction to the beam and provide it to a mass analyzer section of the mass spectrometer. This pulse simultaneously causes non-extracted ions of the beam to be deflected onto an electrode of opposite charge. A pulse ON time is at least twice as long (and optionally even three or four times as long) as required to extract the ion packet and provide it to the mass analyzer section, so as to reduce stray ions entering the mass analyzer section. In one aspect, a series of such pulses are applied as a pulse train such that during pulse ON times ion packets are extracted while other ions of the beam are deflected onto the second electrode.
In one aspect of the method, an ion beam is passed between first and second electrodes and across an opening in the second electrode. A potential difference pulse is applied across the electrodes such that during a pulse ON time, ions of the beam adjacent the opening just before the pulse is applied are extracted through the opening as an ion packet and provided to a mass analyzer section of the mass spectrometer, while other ions of the beam are caused to be deflected onto the second electrode which is oppositely charged from the ions. The pulse ON time may, for example, be at least twice as long as required to extract the ion packet so as to reduce stray ions entering the mass analyzer section. A series of such pulses may be applied as a pulse train such that during pulse OFF times the ion beam passes across the opening, and during pulse ON times ion packets are extracted while other ions of the beam are deflected onto the second electrode.
While various values of pulse ON time may be applied, the pulse ON time may be longer than the pulse OFF time. For example, pulse ON time may be at least twice as long (or four, or even ten times). In one embodiment, the pulse ON time is the time required for ions of a predetermined highest mass of interest to be analyzed by the analyzer section, minus the time required to refill the region of the beam from which the ion packet is extracted with ions of the predetermined highest mass (in some embodiments, the region across the opening). By xe2x80x9cfillingxe2x80x9d or xe2x80x9crefillingxe2x80x9d the region in this context, is referenced that those ions of the predetermined mass have been re-established across the region from which the packets are extracted (in some embodiments, the region across the opening). The relative pulse ON and OFF times are optionally adjusted for the particular mass spectrometer to minimize background.
The present invention further provides a pulser in which one or more methods of the present invention can be executed, so as to provide an ion packet to an analyzer section of a mass spectrometer from an ion beam. The pulser includes a set of electrodes which can maintain an ion beam and to which a potential difference pulse can be applied to extract an ion packet from the beam at a sideways direction to the beam and provide it to a mass analyzer section of the mass spectrometer. The pulse simultaneously causes non-extracted ions of the beam to be deflected onto an electrode of opposite charge. A power supply provides the series of pulses as a pulse train to the electrode set, as described in the method above, so as to reduce stray ions entering the mass analyzer section.
In one aspect, the electrode set includes the first and second electrodes described above. Such electrodes may face one another with a gap between them which is narrower adjacent one side of the opening than at an opposite side of the opening, such that the ion beam can initially pass across the opening from the narrower side to the opposite side. In one configuration the first and second electrodes may be two parallel members with opposed inwardly directed extensions to define the narrower gap on the one side. The present invention further provides a mass spectrometer which includes the pulser and mass analyzer, of a configuration already described.
The various aspects of the present invention can provide any one or more of the following and/or other useful benefits. For example, by using an extraction pulse as described, the leakage of ions into the mass analyzer can be inhibited. As a result, noise at the detector can be reduced. Furthermore, the pulser may be of relatively simple construction.